For each of the five groups of target samples, PRS were normalized and the significance of the case-control score difference was tested by standard logistic regression including principal components. For each target group and for each P-value threshold the proportion of variance explained (i.e. Nagelkerke’s R2) was estimated by comparing the regression with PRS to a reduced model with covariates only. The OR for ADHD within each PRS decile group was estimated based on the normalized score across groups (using the P-value threshold with the highest Nagelkerke’s R2 within each target group) (Figure 3). OR was also estimated using logistic regression on the continuous scores for each target group separately and an OR based on all samples using the normalized PRS score across all groups (Supplementary Figure 9). Additionally PRS were evaluated in the PGC samples using the iPSYCH sample as training sample, following the approach described above (Supplementary Information).